Current Status of LEKTI, a Physiological Inhibitor of Multiple Proteinases in the Skin-A Review

Serine Protease Inhibitor Kazal-type 5 (SPINK5) gene encodes 3 different Lympho-Epithelial Kazal-Type-Inhibitor (LEKTI) isoforms, which differ in their C-terminal sequence, are organized into longer than 15, 15, and 13 inhibitory domains. Pro-LEKTI is processed intracellular and the bioactive LEKTI fragments are secreted. LEKTI shows a restricted expression pattern in skin, thymus, oral mucosa, vaginal epithelium, Bartholin's glands, pituitary, tonsils, and parathyroid glands. Recombinant full-length LEKTI and rLEKTI fragments inhibit the activity of plasmin, subtilisin A, cathepsin G, neutrophil elastase, trypsin, caspase 14, and kallikreins (KLK) 5, 6, 7, 13, and 14 (involved in skin desquamation and growth hormone processing) to varied extents. Loss-of-function mutations, polymorphisms, and transcriptional inactivation of the cognate SPINK5 gene resulting in LEKTI loss or defective LEKTI processing is linked to Netherton syndrome (NS), head and neck squamous cell carcinomas (HNSCC), asthma, and chronic rhinosinusitis. Here, we give a brief review on the published work of LEKTI.